1: Single-cell bioluminescence imaging of deep tissue in freely moving animals.anti-oxidant consumed in cancer survival
Science of the Month - July 2018
Science.
2018 Feb 23;359(6378):935-939. doi: 10.1126/science.aaq1067.
Satoshi Iwano, Mayu Sugiyama, Hiroshi Hama, Akiya Watakabe, Naomi Hasegawa, Takahiro Kuchimaru, Kazumasa Z. Tanaka, Megumu Takahashi, Yoko Ishida, Junichi Hata, Satoshi Shimozono, Kana Namiki, Takashi Fukano, Masahiro Kiyama, Hideyuki Okano, Shinae Kizaka-Kondoh, Thomas J. McHugh, Tetsuo Yamamori, Hiroyuki Hioki, Shojiro Maki, Atsushi Miyawaki*
Viewing fireflies is a classic summer tradition. Fireflies glow due to a bioluminescent system in which an enzyme called Luciferase oxidizes a substrate called D-luciferin. A new imaging system (AkaBLI) has been developed by the group of Atsushi Miyawaki (class of '66), a team leader at RIKEN. This system can detect luminescent signals from deep within animal tissues at an intensity 100 to 1,000 times greater than conventional methods by combining an artificial enzyme (AlaLuc), created by introducing mutations into firefly Luciferase, with an artificial substrate (AkaLumine), synthesized from D-luciferin. With support from AMED's Brain/MINDS program, the group has advanced research into applying AkaBLI to the nervous system. They recently published a paper in *Science* in collaboration with groups including that of Professor Hideyuki Okano (class of '62) from the School of Medicine's Department of Physiology. This study made it possible to non-invasively observe luminescence from labeled nerve cells in the striatum (a subcortical region) of mice that were unanesthetized and freely moving. Similarly, they successfully observed luminescence from nerve cells within the striatum of adult marmosets (a primate species) over a long period. This achievement enables the analysis of higher brain functions in higher animals under more natural conditions and allows for the tracking of smaller numbers of cells in vivo. Applications are expected in the fields of neuroscience and stem cell research.
(Hideyuki Okano, class of '62, Department of Physiology; Atsushi Miyawaki, class of '66, RIKEN Center for Brain Science)
2: Aortic carboxypeptidase-like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis
JOURNAL OF CLINICAL INVESTIGATION,
128 (4):1581-1596; 10.1172/JCI92863 APR 2 2018
Teratani Toshiaki, Tomita Kengo, Suzuki Takahiro, Furuhashi Hirotaka, Irie Rie, Nishikawa Makoto, Yamamoto Junji, Hibi Toshifumi, Miura Soichiro, Minamino Tohru, Oike Yuichi, Hokari Ryota, Kanai Takanori
Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome and is a progressive liver disease that can advance to cirrhosis and liver cancer. With the increase in the obese population, the number of NASH patients is rapidly rising worldwide, making the elucidation of its pathology and the establishment of treatments an urgent issue. This study revealed that the expression of Aortic carboxypeptidase–like protein (ACLP) is specifically enhanced in hepatic stellate cells (the cells responsible for the pathogenesis of liver fibrosis) as NASH progresses. Furthermore, it was discovered that ACLP is a Wnt ligand that activates the β-catenin pathway. In the context of NASH, ACLP was found to be a pro-fibrotic factor that activates hepatic stellate cells by enhancing β-catenin signaling. Additionally, obesity-related factors such as free fatty acids were found to enhance ACLP expression. Although obesity and metabolic syndrome lead to fatty liver, it was previously unclear why the condition progresses to NASH. This research has identified a new Wnt ligand, ACLP, produced by hepatic stellate cells, as the responsible molecule that explains this pathogenic mechanism. It is expected to be a future molecular target for the treatment of NASH, including hepatocellular carcinoma.
(Toshiaki Teratani, equivalent to class of '86, Department of Gastroenterology and Hepatology; Takanori Kanai, class of '67, Department of Gastroenterology and Hepatology; Kengo Tomita, class of '72, Department of Gastroenterology, National Defense Medical College)
Other Published Papers
1: NF-kappa B, inflammation, immunity and cancer: coming of age
NATURE REVIEWS IMMUNOLOGY,
18 (5):309-324; 10.1038/nri.2017.142 MAY 2018
Taniguchi Koji, Karin Michael
2: Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells
BLOOD,
131 (16):1833-1845; 10.1182/blood-2017-05-787226 APR 19 2018
Shima Haruko, Takamatsu-Ichihara Emi, Shino Mika, Yamagata Kazutsune, Katsumoto Takuo, Aikawa Yukiko, Fujita Shuhei, Koseki Haruhiko, Kitabayashi Issay